# Regulation of the Hedgehog Pathway by new cilium proteins in Development and Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, MERCED · 2023 · $323,545

## Abstract

PROJECT SUMMARY
Defects in Hedgehog (Hh) signaling is widely implicated in various birth defects and cancers. The
transduction of Hh signaling relies on the primary cilium, a miniature cell surface organelle known as
the antenna of the cell. To activate Hh signaling, almost all protein transducers need to transit through
the cilium. However, the molecular mechanisms of these protein transportation are not completely
understood; and the signaling cascade within the cilium also remains unclear in the field. Our goal is to
fill this gap with mechanistic studies of novel cilium proteins in the regulation of Hh signaling in vitro and
in vivo. In preliminary studies, we have leveraged a new proximity-labeling tool and built an experimental
platform to discovery new signaling proteins in the cilium with quantitative proteomics. We discovered
surprising cilium localization of a molecule involved in receptor internalization during neural
development. In this proposal, we aim to 1) decipher how the new cilium molecule control protein
transport in the cilium during Hh signal activation; 2) determine its role in the Hh-controlled neural
progenitor proliferation in the developing brain; and 3) apply the proximity biotinylation approach to
identify new proteins involved in Smo trafficking and signaling during the time course of Hh activation.
Our approach is innovative because it will reveal a new function of an old protein in the cilium during
Hh transduction, and it employs a newly developed biotinylation tool to gain the systematic view of
signaling proteins during Hh signaling activation. Upon completion, our study will shed light on long
standing questions in the Hh pathway and may highlight new methods for the intervention of Hh related
developmental disorders.

## Key facts

- **NIH application ID:** 10652622
- **Project number:** 5R01GM143276-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Xuecai Ge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $323,545
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652622

## Citation

> US National Institutes of Health, RePORTER application 10652622, Regulation of the Hedgehog Pathway by new cilium proteins in Development and Disease (5R01GM143276-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10652622. Licensed CC0.

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